Search

Background: Diagnosis of heparin-induced thrombocytopenia (HIT) requires pretest probability assessment and dedicated laboratory assays., Objective: To develop a pretest score for HIT., Design: Observational; analysis of prospectively collected data of hospitalized patients suspected with HIT (ClinicalTrials.gov NCT00748839)., Setting: Thirty-one tertiary hospitals in France, Switzerland, and Belgium., Patients: Patients tested for HIT antibodies (2280 evaluable), randomly allocated to derivation and validation cohorts., Measurements: Independent adjudicators diagnosed HIT based on the prospectively collected data and serotonin release assay results., Results: Heparin-induced thrombocytopenia was diagnosed in 234 (14.7%) and 99 (14.5%) patients in the two cohorts. Eight features were associated with HIT (in brackets, points assigned for score calculation of the score): unfractionated heparin (1); therapeutic-dose heparin (1); cardiopulmonary bypass (cardiac surgery) (2); major trauma (3); 5- to 21-day interval from anticoagulation initiation to suspicion of HIT (4); ≥40% decrease in platelet count over ≤6 days (3); thrombotic event, arterial (3) or venous (3). The C-statistic was 0.79 (95% CI, 0.76-0.82). In the validation cohort, the area under the receiver operating characteristic curve was 0.77 (95% CI, 0.74-0.80). Three groups of scores were defined; HIT prevalence reached almost 30% in the high-probability group., Limitation: The performance of the score may depend on settings and practices., Conclusion: The objective, easy-to-collect, clinical features of HIT we evidenced were incorporated into a pretest score, which may guide clinical decisions regarding diagnostic testing and anticoagulation., (© 2021 International Society on Thrombosis and Haemostasis.)

Background: Anticoagulation during cardiopulmonary bypass (CPB) is usually adapted to total body weight (TBW). This may be inaccurate in obese patients and lead to heparin overdose with a risk of bleeding., Objectives: To validate the efficacy and safety of an adjusted calculation model of heparin dosing based on ideal body weight (IBW) rather than TBW in obese CPB patients, with an expected target mean plasma heparin concentration of 4.5 IU ml after onset of CPB in the experimental group., Design: Randomised controlled study., Setting: University hospital., Patients: Sixty obese patients (BMI ≥ 30 kg m) scheduled for CPB were included from January to June 2016., Interventions: Patients received a bolus dose of unfractionated heparin of either 300 IU kg of TBW or 340 IU kg of IBW before onset of CPB. Additional adjusted boluses were injected to maintain an activated clotting time (ACT) of at least 400 s., Main Outcome Measures: Plasma heparin concentration and ACT were measured at different time points. Total heparin doses and transfusion requirements were recorded., Results: The target heparin concentration of 4.5 IU ml was reached in the IBW group at the onset of CPB and maintained at all time points during CPB. Heparin concentrations were significantly higher in the TBW group after the bolus (6.52 ± 0.97 vs. 4.54 ± 1.13 IU ml, P < 0.001) and after cardioplegia (5.10 ± 1.03 vs. 4.31 ± 1.00 IU ml, P = 0.02). Total heparin doses were significantly higher in the TBW group. Mean ACT was significantly lower in the IBW group but remained over 400 s during CPB. The correlation between heparin and ACT was poor. Peri-operative bleeding and transfusion requirements were comparable. No thrombotic event occurred in the CPB circuit., Conclusion: The current IBW-adjusted regimen of heparin administration may be used efficiently in obese CPB patients, thereby avoiding overdose which cannot be accurately assessed by ACT monitoring alone., Trial Registration: ClinicalTrials.gov identifier: NCT02675647.

Background: The heparin regimen providing anticoagulation during cardiopulmonary bypass (CPB) is usually adapted to total body weight (TBW), but may be inaccurate in obese patients in whom TBW exceeds their ideal body weight., Objectives: The objective is to compare the effects of heparin injection based on TBW on haemostatic parameters between obese and nonobese patients during cardiac surgery and to calculate the optimal heparin regimen., Design: Prospective comparative study., Setting: University hospital., Patients: Two groups of 50 patients (BMI≥ or <30 kg m) were included in the study over a 9-month period in 2013. The study started on 27 February 2013., Interventions: An unfractionated heparin (UFH) bolus of 300 IU kg TBW was injected before initiation of CPB followed by additional doses (50 to 100 IU kg) to maintain a target activated coagulation time (ACT) of at least 400 s., Main Outcome Measures: ACT and plasma heparin concentration were measured at different time points after initiation of, and weaning from CPB., Results: Obese patients received higher initial and total doses of heparin (P < 0.0001). Plasma heparin concentrations were significantly higher in obese patients at each time point (P < 0.001) and reached very high values after the initial bolus (5.90 vs. 4.48 IU ml, P < 0.0001). The relationship between plasma heparin concentration and ACT after the initial bolus was not linear and followed an asymptotic regression curve. Haemoglobin concentration decreased intraoperatively to a greater extent in the obese group (P < 0.001). No significant differences in postoperative bleeding or global transfusion requirements were observed., Conclusion: The standard heparin regimen based on TBW in obese patients during CPB results in excessive plasma heparin concentrations and a significant intraoperative decrease in haemoglobin concentration. ACT monitoring was not accurate in identifying this excess dosage. An initial bolus of 340 IU kg ideal body weight would achieve a heparin concentration of 4.5 IU ml, similar to that observed in nonobese patients. Further investigations are warranted to confirm this heparin regimen.

Introduction: The aim of this study was to collect data in France in patients with heparin-induced thrombocytopenia who required parenteral anticoagulation and for whom other non-heparin anticoagulant therapies were contraindicated including patients with renal failure, cross-reactivity to danaparoid or at high hemorrhagic risk., Methods: A total of 20 patients, of mean age 72 ± 10 years, were enrolled in this open-label, multicenter clinical study. Exploratory statistical data analysis was performed with descriptive interpretation of intra-individual comparisons using simple univariate statistics., Results: The diagnosis of HIT was confirmed in 16 subjects by an independent scientific committee. Fourteen patients (70 %) were in an intensive care unit during the course of the study. Patients were treated with argatroban for a mean duration of 8.5 ± 6.1 days. The mean starting dose of argatroban was 0.77 ± 0.45 μg/kg/min. Platelet recovery was rapid. aPTT and anti-IIa activity assays were used to monitor the dose of argatroban. The mean baseline aPTT value was 45.0 ± 9.8 sec and increased to 78.2 ± 35.8 sec two hours after initiating argatroban. At this time mean argatroban concentration was 0.34 ± 0.16 and 0.61 ± 0.28 μg/ml using ECT and TT measurements, respectively. New and/or extended thromboses were reported in 25 % of patients and major bleedings were documented in 15 %. Six patients died due to their underlying medical condition., Conclusion: Considering its hepatic elimination and its short half-life, argatroban can be considered as a safe therapeutic option in HIT patients at high hemorrhagic risk and with renal failure, particularly in an ICU setting.

Unlabelled: We undertook a survey of French university hospital hematological laboratories to ascertain the clinical characteristics of patients with suspected HIT, the laboratory tests performed, and the therapeutic strategy adopted in current practice., Methods: A standardized medical records database for patients with suspected HIT was sent to 19 laboratories. During two months, all consecutive patients for whom a biological test was performed were included., Results: 169 patients were included, 27 (16%) patients having a final diagnosis of HIT. At the time HIT was suspected, the heparin duration and the level of thrombocytopenia were similar in HIT- positive and HIT-negative groups. The use of unfractionated heparin, a therapeutic heparin dose regimen and the presence of thrombotic complications were significantly more frequent in HIT-positive patients. When the heparin dose regimen was taken into account, only thrombotic complications under a therapeutic dose regimen were significantly increased in HIT-positive patients. Eighty-six percent of patients presented at least one alternative diagnosis of thrombocytopenia without significant difference between the two groups. Laboratory tests were performed after a mean of 0.3days and mainly consisted of antigen assays. At the time HIT was suspected, heparin was stopped in 56 (33%) patients, being replaced mainly by danaparoid. Only three laboratories declared they usually received all the necessary clinical information to establish the likelihood of HIT., Conclusion: In current practice in France, the clinical probability of HIT is rarely established, leading to systematic requests for laboratory HIT tests., (Copyright 2010 Elsevier Ltd. All rights reserved.)

The antithrombotic efficacy of lepirudin in patients with heparin-induced thrombocytopenia (HIT) is compromised by an increased risk for bleeding. A retrospective observational analysis in 181 patients (median age, 67 years) with confirmed HIT treated in routine practice with lepirudin was performed to identify predictive factors for thrombotic and bleeding complications. Lepirudin was administered at a mean (+/- SD) dose of 0.06 +/- 0.04 mg/kg/h (compared with a recommended initial dose of 0.15 mg/kg/h). Mean activated partial thromboplastin time was greater than 1.5 times baseline value in 99.4% of patients. Median treatment duration was 7.7 days. Until discharge from the hospital, 13.8% and 20.4% of patients experienced a thrombotic or a major bleeding event, respectively. On multivariate analysis, mean lepirudin dose was not a significant predictive factor for thrombosis. In contrast, mean lepirudin dose greater than 0.07 mg/kg/h, long duration of lepirudin treatment, and moderate to severe renal impairment were significant positive factors for major bleeding. Overall, these results suggest that the recommended dose of lepirudin in patients with HIT is too high; the use of reduced doses may be safer with regard to bleeding risk and does not compromise antithrombotic efficacy.

Eighty patients undergoing pelvic or abdominal surgery for cancer were randomized in two groups for prevention of postoperative thromboembolism: 40 patients received a 15,000 IU day-1 Calciparine prophylaxis and 40 patients a 5000 anti-Xa U/d Fragmin prophylaxis for 10 days. In the Calciparine group, two patients (5%) developed postoperative pulmonary embolism but none developed it in the Fragmin group. Two patients in the Fragmin group (5%) developed isotopic DVT, which was not confirmed by phlebography. There was no deep vein thrombosis of the lower limbs in the two groups. Important postoperative bleeding (one patient in the Calciparine group and two patients in the Fragmin group) was similar in both groups. Moderate and minor bleeding were significantly lower in the Fragmin group. Haemoglobin and haematocrit changes, total blood loss and transfusion requirements were not different in both groups. It is concluded that, over a 10-day period, one daily 5000 U Fragmin prophylaxis was as effective and safe as three daily 5000 IU Calciparine injections.

Low molecular weight heparins have stimulated much interest because of their supposedly more selective action on Xa factor. A randomized study in 50 patients compared efficacy of low doses of a standard heparin, calciparin (5,000 IU/8 h) with that of a low molecular weight heparin, fragmine (Kabi 2165) (5,000 anti-Xa U/24 h), in the prophylaxis of postoperative thrombosis after oncologic surgery. Three of 25 patients receiving calciparin developed pulmonary embolism, as against one of 25 treated with fragmine who developed a periphlebitis. Hemorrhagic complications were comparable in the two groups. Anti-Xa activity was significantly higher in the fragmine group, whereas platelet counts, cephalin times with activator and anti-IIa activity were similar. These findings indicate equal efficacy of fragmine and calciparin in the prophylaxis of post-oncology surgery venous thrombosis.